Project Summary/Abstract The long term goal of this project is to determine the likely health effects in Smokers with Mental Health Conditions (SMHC) of a rule requiring very low nicotine content in cigarettes, in conjunction with availability of nicotine-containing electronic cigarettes (ecigs). This will be tested in a rigorous randomized controlled trial design. We plan to use a comprehensive set of measures of proven validity and reproducibility, including toxicant exposure (urinary NNAL, exhaled CO), addiction (FTND) and mental health (Kessler K6) to assess these effects. This is a prospective parallel-group randomized double-blind, 2-by-2 controlled trial in which 240 current smokers with mental health conditions will be randomized to one of 4 groups: 1) normal nicotine content cigarettes (11mg nicotine content per cigarette, NNCs) and 15mg/mL nicotine ecigs; 2) NNCs and zero mg/mL nicotine ecigs; 3) Very low nicotine content cigarettes (0.2mg nicotine/cigarette, VLNCs) and 15mg/mL nicotine ecigs 4) VLNCs and zero mg/mL nicotine ecigs. They will be followed for 16 weeks on study products and then another 4 weeks thereafter. Participants will first complete a preliminary phone eligibility assessment and an in-person screening. Next, an in person assessment visit will be scheduled to complete informed consent and determine eligibility. After 1 week of smoking their own brand of cigarettes, participants will receive 2 weeks of the NNC cigarettes and be asked to keep a cigarette log. Eligible participants will be randomly assigned to one of the four groups using a computer algorithm developed by study statisticians and overseen by the Penn State Investigational Drug Pharmacy. The Pharmacy will also prepare blinded cigarettes and e-cig devices. All study products will be relabeled to ensure participants and staff are blinded to the nicotine content. At the end of the 16-week randomization phase, participants will come to their last visit, receive encouragement to quit all tobacco products and be given resources in the community where they can receive smoking cessation counseling. Participants will be asked to provide information about their intentions for ongoing tobacco product use or cessation and will be followed up 4 weeks later to assess these outcomes. Those claiming to be no longer using combustible tobacco products will be visited to verify with a measure of exhaled CO.